title: Angiotensin receptor blockers and statins could alleviate atrial fibrosis via regulating platelet-derived growth factor/Rac1/nuclear factor-kappa B Axis.
abstract: OBJECTIVE
  To investigate whether the administration of renin-angiotensin system (RAS) inhibitors and statins could alleviate atrial fibrosis via platelet-derived growth factor (PDGF)/Rac1 /nuclear factor-kappa B (NF-κB) axis.
  
  
  RESULTS
  In human left atrium, the degree of atrial fibrosis, as well as the expression levels of PDGF, Rac1 and NF-κB increased 1.5 to 2.9 folds in patients with atrial fibrillation compared to that with sinus rhythm, (P<0.0001). There were strongly positive correlations between angiotensin II (Ang II) or procollagen type III-alpha-1 (COL3A1) with PDGF, Rac1, NF-κB, and among PDGF, Rac1 and NF-κB (all P<0.05). At 3 weeks after the transverse aorta constriction (TAC) operation in rat model and with intervention of irbesartan or/and simvastatin, the collagen volume fraction (CVF) and atrial natriuretic peptide (ANP) values respectively increased 6-folds and 3.5-folds in the TAC group compared to SHAM group (P<0.0001), but these levels decreased by 16% to 63% with following drug intervention (all P<0.0001), the combined treatment was the lowest. Accordingly, the expression levels of PDGF (3-folds), Rac1 (1.6-folds), NF-κB (7-folds) and AngII (12-folds) significantly increased in the TAC group compared to the SHAM group, and these levels were also reduced by 25% to 64% with following drug intervention. The highest reduction could be seen after treatment with irbesartan and simvastatin in combination (all P<0.001).There were strongly positive correlations between AngII or CVF with PDGF, Rac1, NF-κB, and among PDGF, Rac1 and NF-κB (all P<0.05).
  
  
  CONCLUSIONS
  Irbesartan or/and simvastatin can improve atrial fibrosis by regulating PDGF/Rac1/NF-κB axis.
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Dongfang
authors.initials: D
authors.lastname: Yang
authors.forename: Jia
authors.initials: J
authors.lastname: Yuan
authors.forename: Gan
authors.initials: G
authors.lastname: Liu
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Ling
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zeng
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: She
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D057911:Angiotensin Receptor Antagonists; D017931:DNA Primers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D010982:Platelet-Derived Growth Factor; D000804:Angiotensin II; D020830:rac1 GTP-Binding Protein
keywords: Irbesartan; Rac1; Simvastatin.; atrial fibrosis; nuclear factor-kappa B (NF-κB); platelet-derived growth factor (PDGF)